B-cell non-Hodgkin lymphoma: Selective vulnerability to PIKFYVE inhibition.
Autophagy
; 13(6): 1082-1083, 2017 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-28350209
ABSTRACT
We identified the PIKFYVE inhibitor apilimod as a potent and selective cytotoxic agent against B-cell non-Hodgkin lymphoma (B-NHL). Our data robustly establish PIKFYVE as the target through which apilimod kills B-NHL cells and show that apilimod-induced death in B-NHL is mediated by broad disruption of lysosome homeostasis characterized by lysosomal swelling, TFEB nuclear translocation, impaired maturation of lysosomal enzymes and incomplete autophagosome clearance. Furthermore, through genome-wide CRISPR knockout screening, we identified specific lysosomal genes (TFEB, CLCN7, OSTM1 and SNX10) as critical determinants of apilimod-induced cytotoxicity. Together these data highlight disruption of lysosome homeostasis through PIKFYVE inhibition as a novel anticancer mechanism in B-NHL and potentially other cancers.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfoma não Hodgkin
/
Linfócitos B
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Inibidores de Proteínas Quinases
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Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Humans
Idioma:
En
Revista:
Autophagy
Ano de publicação:
2017
Tipo de documento:
Article